The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Paul Kosma - One of the best experts on this subject based on the ideXlab platform.
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crystal and molecular structure of methyl l glycero α d manno heptopyranoside and synthesis of 1 7 linked l glycero d manno heptobiose and its methyl α glycoside
Carbohydrate Research, 2011Co-Authors: Daniel Artner, Christian Stanetty, Kurt Mereiter, Alla Zamyatina, Paul KosmaAbstract:Methyl l-glycero-α-d-manno-heptopyranoside was synthesized in good yield by a Fischer-type glycosylation of the heptopyranose with methanol in the presence of cation-exchange resin under reflux and microwave conditions, respectively. The compound crystallized from 2-propanol in an orthorhombic lattice of space group P21212 showing a comparatively porous structure with a 2-dimensional O–H⋯O hydrogen bond network. As model compounds for the side chain domains of the inner core structure of bacterial lipopolysaccharide, l-glycero-α-d-manno-heptopyranosyl-(1→7)-l-glycero-d-manno-heptopyranose and the corresponding disaccharide methyl α-glycoside were prepared. The former compound was generated via glycosylation of a benzyl 5,6-dideoxy-hept-5-enofuranoside intermediate followed by catalytic Osmylation and deprotection. The latter disaccharide was efficiently synthesized in good yield by a straightforward coupling of an acetylated N-phenyltrifluoroacetimidate heptopyranosyl donor to a methyl 2,3,4,6-tetra-O-acetyl heptopyranoside acceptor derivative followed by Zemplen deacetylation.
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A short synthesis of D-glycero-D-manno-heptose 7-phosphate.
Carbohydrate research, 2005Co-Authors: Hacer Güzlek, Andrea Graziani, Paul KosmaAbstract:d-glycero-d-manno-Heptopyranose 7-phosphate—an intermediate in the biosynthesis of nucleotide-activated heptoses—has been prepared in good overall yield from benzyl 5,6-dideoxy-2,3-O-isopropylidene-α-d-lyxo-(Z)-hept-5-enofuranoside by a short-step synthesis. Phosphitylation using the phosphoramidite procedure followed by in situ oxidation afforded the corresponding 7-O-phosphotriester derivative in high yield. Subsequent Osmylation proceeded in good diastereoselectivity (4:1) to furnish the d-glycero-d-manno-configured derivative, which was separated from the l-glycero-l-gulo-isomer by chromatography. Hydrogenolysis led to simultaneous removal of the benzyl and isopropylidene groups and afforded the target compound in high yield, which serves as a substrate of bacterial heptose 7-phosphate kinases.
Jacques Streith - One of the best experts on this subject based on the ideXlab platform.
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synthesis of 1 6 dideoxynojirimycin 1 6 dideoxy d allo nojirimycin and 1 6 dideoxy d gulo nojirimycin via asymmetric hetero diels alder reactions
ChemInform, 1996Co-Authors: A Defoin, Herve Sarazin, Jacques StreithAbstract:Asymmetric Diels-Alder reaction of sorbaldehyde O-methyloxime 1d with chiral chloronitroso derivative 2 of D-mannose, followed by Osmylation of the primary cycloadduct, led to diol 6a with excellent enantioselectivity (ee > 99%; Scheme 1). Catalytic hydrogenolysis of 6a gave 1,6-dideoxy-D-allo-nojirimycin (7a). Nucleophilic ring opening of cyclic sulfate 8 allowed a straightforward synthesis of 1,6-dideoxynojirimycin (11) and of 1,6-dideoxy-D-gulo-nojirimycin (12; Scheme 2).
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de novo asymmetric synthesis of two 5 amino 5 6 dideoxy d allose derivatives
Tetrahedron Letters, 1994Co-Authors: A Defoin, Herve Sarazin, Christiane Strehler, Jacques StreithAbstract:Abstract Diels-Alder cycloaddition of sorbic aldehyde derivative 9 and of sorbic acid 10 with the chiral chloro-nitroso dienophile 7 led with excellent regio- and diastereoselectivity to the chiral cycloadducts 11a and 12 , respectively. Catalytic Osmylation of their Bzl-derivatives 11b and 13b , followed by reductive cleavage of the NO bonds, gave ultimately the chiral aminoallose derivatives D-5 and D-6 which are potential glycosidase inhibitors.
Anastassia Kanavarioti - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH ARTICLE Osmium-Based Pyrimidine Contrast Tags for Enhanced Nanopore-Based DNA Base Discrimination
2016Co-Authors: Robert Y. Henley, Ana G. Vazquez-pagan, Michael Johnson, Anastassia Kanavarioti, Meni WanunuAbstract:Nanopores are a promising platform in next generation DNA sequencing. In this platform, an individual DNA strand is threaded into nanopore using an electric field, and enzyme-based ratcheting is used to move the strand through the detector. During this process the residual ion current through the pore is measured, which exhibits unique levels for different base combinations inside the pore. While this approach has shown great promise, accuracy is not optimal because the four bases are chemically comparable to one another, leading to small differences in current obstruction. Nucleobase-specific chemical tagging can be a via-ble approach to enhancing the contrast between different bases in the sequence. Herein we show that covalent modification of one or both of the pyrimidine bases by an osmium bipyri-dine complex leads to measureable differences in the blockade amplitudes of DNA mole-cules. We qualitatively determine the degree of Osmylation of a DNA strand by passing it through a solid-state nanopore, and are thus able to gauge T and C base content. In addi-tion, we show that osmium bipyridine reacts with dsDNA, leading to substantially different current blockade levels than exhibited for bare dsDNA. This work serves as a proof of princi-ple for nanopore sequencing and mapping via base-specific DNA Osmylation
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False positives and false negatives measure less than 0.001% in labeling ssDNA with osmium tetroxide 2,2’-bipyridine
Beilstein-Institut, 2016Co-Authors: Anastassia KanavariotiAbstract:Osmium tetroxide 2,2’-bipyridine (OsBp) is known to react with pyrimidines in ssDNA and preferentially label deoxythymine (T) over deoxycytosine (C). The product, osmylated DNA, was proposed as a surrogate for nanopore-based DNA sequencing due to OsBp’s “perfect” label attributes. Osmylated deoxyoligos translocate unassisted and measurably slow via sub-2 nm SiN solid-state nanopores, as well as via the alpha-hemolysin (α-HL) pore. Both nanopores discriminate clearly between osmylated and intact nucleobase; α-HL was also shown to discriminate between osmylated T and osmylated C. Experiments presented here confirm that the kinetics of Osmylation are comparable for short oligos and long ssDNA and show that pyrimidine Osmylation is practically complete in two hours at room temperature with less than 15 mM OsBp. Under the proposed labeling conditions: deoxyoligo backbone degradation measures less than 1/1,000,000; false positives such as osmylated deoxyadenine (A) and osmylated deoxyguanine (G) measure less than 1/100,000; false negatives, i.e., unosmylated C measure less than 1/10,000; and unosmylated T must measure substantially lower than 1/10,000 due to the 27-fold higher reactivity of T compared to C. However, osmylated C undergoes degradation that amounts to about 1–2% for the duration of the labeling protocol. This degradation may be further characterized, possibly suppressed, and the properties of the degradation products via nanopore translocation can be evaluated to assure base calling quality in a DNA sequencing effort
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Single pyrimidine discrimination during voltage-driven translocation of osmylated oligodeoxynucleotides via the α-hemolysin nanopore
Beilstein-Institut, 2016Co-Authors: Yun Ding, Anastassia KanavariotiAbstract:The influence of an electric field on an isolated channel or nanopore separating two compartments filled with electrolytes produces a constant ion flux through the pore. Nucleic acids added to one compartment traverse the pore, and modulate the current in a sequence-dependent manner. While translocation is faster than detection, the α-hemolysin nanopore (α-HL) successfully senses base modifications in ssDNA immobilized within the pore. With the assistance of a processing enzyme to slow down translocation, nanopore-based DNA sequencing is now a commercially available platform. However, accurate base calling is challenging because α-HL senses a sequence, and not a single nucleotide. Osmylated DNA was recently proposed as a surrogate for nanopore-based sequencing. Osmylation is the addition of osmium tetroxide 2,2’-bipyridine (OsBp) to the C5–C6 pyrimidine double bond. The process is simple, selective for deoxythymidine (dT) over deoxycytidine (dC), unreactive towards the purines, practically 100% effective, and strikingly independent of length, sequence, and composition. Translocation of an oligodeoxynucleotide (oligo) dA10XdA9 via α-HL is relatively slow, and exhibits distinct duration as well as distinct residual current when X = dA, dT(OsBp), or dC(OsBp). The data indicate that the α-HL constriction zone/β-barrel interacts strongly with both OsBp and the base. A 23 nucleotide long oligo with four dT(OsBp) traverses 18-times slower, and the same oligo with nine (dT+dC)(OsBp) moieties traverses 84-times slower compared to dA20, suggesting an average rate of 40 or 180 μs/base, respectively. These translocation speeds are well above detection limits, may be further optimized, and clear the way for nanopore-based sequencing using osmylated DNA
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Translocation statistics for 20-mer ssDNA with various Osmylation levels.
2015Co-Authors: Robert Y. Henley, Ana G. Vazquez-pagan, Michael Johnson, Anastassia Kanavarioti, Meni WanunuAbstract:Histograms of the fractional current blockade (left) and the log of the dwell time (right) for several 20-mer single-stranded DNA samples (see text). The fractional current blockades increase with the degree of T-content upon Osmylation, while similarly; dwell times increase with Osmylation levels.
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Translocation events for an 80-mer fragment after R1 and R2 reactions.
2015Co-Authors: Robert Y. Henley, Ana G. Vazquez-pagan, Michael Johnson, Anastassia Kanavarioti, Meni WanunuAbstract:(a) Histograms are shown for the fractional current blockade as well as the dwell times for 80-mer ssDNA with varying degrees of Osmylation passing through a SiN nanopore with an applied bias voltage of 300mV. T+C osmylated molecules show markedly greater dwell times as compared to unreacted and T-osmylated molecules. The red stars indicate all of the lower blockade peaks of the double Gaussian fits, which correspond to collision events; green, blue, and black stars indicate the locations of the higher blockade translocation peaks for each distribution. (b) Concatenated events are shown for each molecule. Data is shown after low-pass filtering at 100 kHz.
Meni Wanunu - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH ARTICLE Osmium-Based Pyrimidine Contrast Tags for Enhanced Nanopore-Based DNA Base Discrimination
2016Co-Authors: Robert Y. Henley, Ana G. Vazquez-pagan, Michael Johnson, Anastassia Kanavarioti, Meni WanunuAbstract:Nanopores are a promising platform in next generation DNA sequencing. In this platform, an individual DNA strand is threaded into nanopore using an electric field, and enzyme-based ratcheting is used to move the strand through the detector. During this process the residual ion current through the pore is measured, which exhibits unique levels for different base combinations inside the pore. While this approach has shown great promise, accuracy is not optimal because the four bases are chemically comparable to one another, leading to small differences in current obstruction. Nucleobase-specific chemical tagging can be a via-ble approach to enhancing the contrast between different bases in the sequence. Herein we show that covalent modification of one or both of the pyrimidine bases by an osmium bipyri-dine complex leads to measureable differences in the blockade amplitudes of DNA mole-cules. We qualitatively determine the degree of Osmylation of a DNA strand by passing it through a solid-state nanopore, and are thus able to gauge T and C base content. In addi-tion, we show that osmium bipyridine reacts with dsDNA, leading to substantially different current blockade levels than exhibited for bare dsDNA. This work serves as a proof of princi-ple for nanopore sequencing and mapping via base-specific DNA Osmylation
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Translocation statistics for 20-mer ssDNA with various Osmylation levels.
2015Co-Authors: Robert Y. Henley, Ana G. Vazquez-pagan, Michael Johnson, Anastassia Kanavarioti, Meni WanunuAbstract:Histograms of the fractional current blockade (left) and the log of the dwell time (right) for several 20-mer single-stranded DNA samples (see text). The fractional current blockades increase with the degree of T-content upon Osmylation, while similarly; dwell times increase with Osmylation levels.
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Translocation events for an 80-mer fragment after R1 and R2 reactions.
2015Co-Authors: Robert Y. Henley, Ana G. Vazquez-pagan, Michael Johnson, Anastassia Kanavarioti, Meni WanunuAbstract:(a) Histograms are shown for the fractional current blockade as well as the dwell times for 80-mer ssDNA with varying degrees of Osmylation passing through a SiN nanopore with an applied bias voltage of 300mV. T+C osmylated molecules show markedly greater dwell times as compared to unreacted and T-osmylated molecules. The red stars indicate all of the lower blockade peaks of the double Gaussian fits, which correspond to collision events; green, blue, and black stars indicate the locations of the higher blockade translocation peaks for each distribution. (b) Concatenated events are shown for each molecule. Data is shown after low-pass filtering at 100 kHz.
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Osmium-Based Pyrimidine Contrast Tags for Enhanced Nanopore-Based DNA Base Discrimination.
Public Library of Science (PLoS), 2024Co-Authors: Robert Y. Henley, Ana G. Vazquez-pagan, Michael Johnson, Anastassia Kanavarioti, Meni WanunuAbstract:Nanopores are a promising platform in next generation DNA sequencing. In this platform, an individual DNA strand is threaded into nanopore using an electric field, and enzyme-based ratcheting is used to move the strand through the detector. During this process the residual ion current through the pore is measured, which exhibits unique levels for different base combinations inside the pore. While this approach has shown great promise, accuracy is not optimal because the four bases are chemically comparable to one another, leading to small differences in current obstruction. Nucleobase-specific chemical tagging can be a viable approach to enhancing the contrast between different bases in the sequence. Herein we show that covalent modification of one or both of the pyrimidine bases by an osmium bipyridine complex leads to measureable differences in the blockade amplitudes of DNA molecules. We qualitatively determine the degree of Osmylation of a DNA strand by passing it through a solid-state nanopore, and are thus able to gauge T and C base content. In addition, we show that osmium bipyridine reacts with dsDNA, leading to substantially different current blockade levels than exhibited for bare dsDNA. This work serves as a proof of principle for nanopore sequencing and mapping via base-specific DNA Osmylation
Barry K Sharpless - One of the best experts on this subject based on the ideXlab platform.
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toward an understanding of the high enantioselectivity in the osmium catalyzed asymmetric dihydroxylation 4 electronic effects in amine accelerated Osmylations
Journal of the American Chemical Society, 1997Co-Authors: Derek W Nelson, Andreas Gypser, Hartmuth C Kolb, Teruyuki Kondo, Hoilun Kwong, Dominic V Mcgrath, Erik A Rubin, Perola Norrby, Kevin P Gable, Barry K SharplessAbstract:Electronic effects in Osmylation reactions accelerated by pyridine and quinuclidine derivatives were investigated by varying the substituents on the amine ligand as well as on the alkene substrate. Ligand substituent effects were gauged by determination of the equilibrium constants for coordination of the amines to OsO4, evaluation of structural properties and reduction potentials of the amine−OsO4 complexes, and analysis of the kinetics of Osmylations in the presence of the amines. Substrate substituent effects were gauged by kinetic Hammett studies using several different amine/alkene combinations. Nonlinear Hammett relationships resulting from alkene substituent effects were observed, and the deviation from a linear free energy relationship was found to depend on the structure, binding capacity, and concentration of the amine. The results were evaluated in terms of the contending “[3 + 2]” and “[2 + 2]” mechanisms currently under consideration. A change in mechanism that depends on the structural and e...
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study of the regio and enantioselectivity of the reactions of osmium tetroxide with allylic alcohols and allylic sulfonamides
Tetrahedron Letters, 1994Co-Authors: Christine Y Park, Barry K SharplessAbstract:Abstract The regioselectivities of the Osmylation of geraniol, its derivatives and geranyl sulfonamides suggest the presence of a moderate attractive interaction between OsO 4 and the allylic groups bearing acidic protons. This allylic directing effect may be due to the development of a hydrogen bonding interaction between OsO 4 and the substrates during the Osmylation process. The potential for a hydrogen bond can also have a substantial effect on the enantioselectivities of the osmium tetroxide catalyzed asymmetric dihydroxylation of allylic alcohols.
